Molecular population genetics and selection in the glycolytic pathway

Abstract

SummaryIn this review, I discuss the evidence for differential natural selection acting across enzymes in the glycolytic pathway in Drosophila. Across the genome, genes evolve at very different rates and possess markedly varying levels of molecular polymorphism, codon bias and expression variation. Discovering the underlying causes of this variation has been a challenge in evolutionary biology. It has been proposed that both the intrinsic properties of enzymes and their pathway position have direct effects on their molecular evolution, and with the genomic era the study of adaptation has been taken to the level of pathways and networks of genes and their products. Of special interest have been the energy-producing pathways. Using both population genetic and experimental approaches, our laboratory has been engaged in a study of molecular variation across the glycolytic pathway in Drosophila melanogaster and its close relatives. We have observed a pervasive pattern in which genes at the top of the pathway, especially around the intersection at glucose 6-phosphate, show evidence for both contemporary selection, in the form of latitudinal allele clines, and inter-specific selection, in the form of elevated levels of amino acid substitutions between species. To further explore this question, future work will require corroboration in other species, expansion into tangential pathways, and experimental work to better characterize metabolic control through the pathway and to examine the pleiotropic effects of these genes on other traits and fitness components.

Genetic perturbation of key central metabolic genes extends lifespan in Drosophila and affects response to dietary restriction

“…The long-term goal of our studies is to integrate geographical and seasonal variation in metabolic genes with life-history phenotypes, such as longevity and its fitness correlates [42]. In this report, we use matched sets of P-element excision alleles in D. melanogaster to create genotypes that possess modest reductions in gene expression and subsequently examine the impact of these perturbations on lifespan under normal and restricted diets.…”

Microevolution of intermediary metabolism: evolutionary genetics meets metabolic biochemistry

“…Because of space considerations I will only briefly summarize two of the most important examples: (1) alcohol dehydrogenase and lipid metabolism, and (2) enzyme polymorphisms at the glucose 6-phosphate (G6P) branchpoint and lipid and glycogen metabolism. This latter example is discussed in detail by Eanes in this issue (Eanes, 2011) and by Zera and Harshman (Zera and Harshman, 2011).…”

“…However, given the often non-linear, hyperbolic relationship between enzyme activity and pathway flux (Kacser and Burns, 1979;Kacser and Burns, 1981;Dykuizen and Dean, 1990), in which a large change in enzyme activity often produces only a small change in flux, such allozyme-dependent modulation of flux is by no means certain. This realization brought investigation of allozymes and pathway flux to the forefront in evolutionary studies of allozyme function, and this refocusing on pathways of metabolism has continued up to the present day Eanes, 1999;Eanes, 2011;Dykhuizen and Dean, 2009).…”

“…Pathways of intermediary metabolism are prime examples of networks and there has been increasing interest in the evolution of systemic properties of metabolic pathways [e.g. the evolutionary changes in glycolytic flux (Eanes et al, 2006;Eanes, 2011)], as well as the influence of pathway properties on the evolution of pathway components [e.g. rate of evolution of an enzyme can be dependent upon its pathway position; e.g.…”

“…This information, in turn, has provided the opportunity to investigate evolutionary changes in whole pathways, which has made an important contribution to the increased interest in adaptive changes in pathways of metabolism (Frera et al, 1999;Gracey and Cossins, 2003;van Strallen and Roelofs, 2006;Larracuente et al, 2007;Greenburg et al, 2008;Matzkin and Markow, 2009;St-Cyr et al, 2008;Eanes, 2011). In the following section, I focus on five prominent areas of recent research on the microevolution of intermediary metabolism.…”